The first step of melanosome transfer from melanocytes to surrounding keratinocytes is successful melanocytic dendrite formation and extension towards surrounding keratinocytes. The extension of melanocytic dendrites requires the reorganization of the melanocyte cytoskeletal elements such as actin filaments and microtubules. Small GTPases Rho, Rac and Cdc42 play a pivotal role in cell morphology and dendrite formation. Specifically, Rac stimulates membrane ruffling and lamellipodia formation, Rho activates dendrite retraction and Cdc42 mediates filopodia and peripheral actin microspike formation.

Ito et al. has shown that treatment of melanocyte and keratinocyte co-cultures with methylophiopogonanone B (5,7-dihydroxy-6,8-dimethyl-3-(4-methoxybenzyl)chroman-4-one, MOPB), an agent reported to activate Rho and induce microtubule disorganization and tubule depolymerization, appeared to reduce melanosome transfer. The authors also showed that treatment with 1μM MOPB did not influence melanin synthesis or the expression of melanogenic enzymes. MOPB appeared to induce a reversible dendrite retraction and transfer inhibition without associated cytotoxicity (tested up to 72 hours).

Centaureidin (5,7,3’-trihydroxy-3,6,4’-trimethoxyflavone), a flavonoid glucoside derived from yarrow, also reduces melanosomal transfer to keratinocytes. Centaureidin is believed to directly or indirectly activate Rho, leading to melanocyte dendrite retraction without influencing melanogenic enzyme expression or melanin synthesis. More analysis is needed to confirm the applicability of MOPB and centaureidin as skin lightening agents.